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Issue 7, 2018
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A versatile method for the selective core-crosslinking of hyaluronic acid nanogels via ketone-hydrazide chemistry: from chemical characterization to in vivo biodistribution

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Abstract

The development of biopolymer-based nanogels has gained particular interest to achieve successful delivery of therapeutics for the treatment of various diseases, such as cancer, infection and diabetes. Herein, we report a new and simple methodology for the covalent stabilization of self-assembled gel nanoparticles based on hyaluronic acid (HA) modified with a thermoresponsive ketone-functional copolymer. This relies on the selective formation of hydrazone crosslinks with bishydrazides within the globular domains of the copolymer chains formed above the cloud point temperature. This approach allows tuning of the crosslinking density by varying the dihydrazide crosslinker to ketone molar ratio. The size distributions and morphology of the nanogels were assessed using dynamic light scattering (DLS), cryo-transmission and scanning electron microscopy. In vitro cellular uptake in several cancer cells and in vivo biodistribution of the nanogels in different mouse tumor models were then explored to assess the effectiveness of this crosslinking strategy. The data from these experiments show prolonged blood circulation, longer than 24 hours, for the crosslinked nanogels and high tumor accumulation.

Graphical abstract: A versatile method for the selective core-crosslinking of hyaluronic acid nanogels via ketone-hydrazide chemistry: from chemical characterization to in vivo biodistribution

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Publication details

The article was received on 09 Apr 2018, accepted on 01 Jun 2018 and first published on 06 Jun 2018


Article type: Paper
DOI: 10.1039/C8BM00396C
Citation: Biomater. Sci., 2018,6, 1754-1763
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    A versatile method for the selective core-crosslinking of hyaluronic acid nanogels via ketone-hydrazide chemistry: from chemical characterization to in vivo biodistribution

    F. P. Garcia, M. Rippe, M. V. P. Companhoni, T. F. Stefanello, B. Louage, S. Van Herck, L. Sancey, J. Coll, B. G. De Geest, C. Vataru Nakamura and R. Auzély-Velty, Biomater. Sci., 2018, 6, 1754
    DOI: 10.1039/C8BM00396C

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